Preparation of certain 2-amino-5-cyanobenzoic acids and their utility as intermediates for preparing corresponding insecticidal cyanoanthranilic diamides has been disclosed (see e.g., Scheme 9 in PCT Patent Publication WO 2004/067528; Scheme 9 and Example 2, Step A in PCT Patent Publication WO 2006/068669; and Scheme 15 and Example 6, Step B in PCT Patent Publication WO 2006/062978).
Maligres et al., Tetrahedron Lett. 1999, 40, 8193 discloses a method for aromatic cyanation via bromide replacement using a Pd catalyst and Zn(CN)2. PCT Patent Publication WO 2006/062978 discloses in Example 6, Step B the preparation of 2-amino-5-cyano-N,3-dimethylbenzamide by palladium-catalyzed cyanation using Zn(CN)2 in N,N-dimethylformamide (DMF) as solvent. Because DMF is a high boiling, water-soluble solvent, it is not easily recycled.
Furthermore, cyanation using an alkali metal cyanide, such as potassium or sodium cyanide, would be less costly and would simplify purification of the final product. These salts, however, are more likely to deactivate metal catalysts and also more sensitive to choice of catalysts and solvent. Therefore Zn(CN)2 is the metal cyanide most commonly used for palladium-catalyzed cyanation. A literature report of using potassium cyanide instead is Sundermeier et al., Chem. Eur. J. 2003, 9 (8), 1828-36, which discloses the cyanation of certain chloroarenes with a Pd catalyst and KCN at high temperatures and in the presence of at least 20 mol % of an amine as co-catalyst.
A need remains for versatile cyanation methods that can perform both Cl and Br replacement to prepare 2-amino-5-cyanobenzoic acid derivatives, do not require high temperatures or reaction-promoting co-catalysts, use easily recycled solvents and use cyanation agents that do not contain heavy metals.